Pro-oxidant response

Using the same experimental conditions, we measured hydroxyl radical formation, using radical trap DMPO, for both DHI-melanin and melanoma cells in culture.(25) The con arison was telling for both, addition of CAT decreased the signal, while SOD caused a large increase in the hydroxyl-radical adduct. Our hypothesis is that the pro-oxidant response in both chemical and cell culture studies are due to the pro-oxidant reactivity of melanin. 

In recent years, numerous papers have been published about one of the most important groups of phytochemicals, the polyphenols (Manach and others 2004). These compounds, which possess an array of healthy properties, but also some disadvantages that will be discussed in this chapter, are present in a variety of plants used in both human and animal diets. However, the structure of this type of compound means that they can be oxidized by several pro-oxidant agents. The objective of this chapter is to describe the main enzymatic agents responsible for the degradation of polyphenols. In order to understand the mechanisms of degradation that will be described in the following sections, a brief summary of the main properties of the polyphenols is required. 

To set up and validate the in vitro systems we initiated a study with rat Uver slices. Stimulation by Upopolysaccharide (LPS) in liver slices was used to evoke a pro-inflammatory response in the Uver. Lipopolysaccharide (LPS), a component of Gram-negative bacterial ceU walls (also called endotoxin), has been associated with tissue injury and sepsis. In the Uver LPS activates the resident macrophages, the Kupffer ceUs, which results in cytokine release [96]. Furthermore, LPS is cleared by the Uver, mainly by Kupffer ceUs [97]. One of the major features of endotoxic shock is the induction of nitric oxide S5mthase in the Uver [98]. Inducible nitric oxide synthase (iNOS), the expression of which is induced by LPS and cytokines, produces nitric oxide (NO) in large quantities [99]. 

Calligaris et al. (2004) studied changes in antioxidant and pro-oxidant activity in milk subjected to different heat treatments. Their results indicated that short heat treatments can be potentially responsible for a depletion in the overall antioxidant properties of milk. Only the application of severe heat treatments, associated with the formation of brown melanoidins, allowed a recovery and even a possible increase in the antioxidant properties of milk. 

The failure of antioxidant mechanisms to correct redox disequilibrium could lead to the escalation of oxidative to tier 2. Tier 2 cellular responses are characterized by the activation of cellular signaling pathway such as stress-activated kinases (p38 MAP kinase and JNK) along with activation and nuclear translocation of transcription factors NF-kB and STAT-1. NF-KB-induced transcriptional activation leads to the production of a number of pro-inflammatory cytokines, including the neutrophil chemoattractant IL-8. STAT-1 activation stimulates the increased production of CXC-motif chemokines that function in lymphocyte recruitment and activation. Therefore, tier 2 oxidative responses result in an inflammatory response in the lung. 

The innate pro-inflammatory response of these cells is activated upon exposure to LPS, prostaglandin or other TLR ligands, leading to production of classical proinflammatory cytokines including tumor necrosis factor (TNF)-a. On the other hand, classical activation by interferon (fFN)- /andLPS leads to production of TNF-a and also increased secretion of reactive oxygen species (ROS) and inducible nitric oxide synthase (iNOS). 

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